The reversion frequencies of most genetically-altered bacterial pathogens preclude their use as live vaccines. We propose to solve this problem by introducing multiple mutations of identical phenotype into a single strain. The reversion frequency of such a strain will be the product of the reversion rates of the individual mutations. Hence, reversion rates of 10 to the minus 21 power can be achieved, making the strain safe. We have demonstrated the feasibility of this approach by constructing a strain of Heamophilus influenzae with three temperature-sensitive mutations of identical phenotype. We plan to exploit this technology and construct a number of H. influenzae type b strains with vaccine potential and evaluate their efficacy in experimental animals.